Researchers at the National Institutes of Health (NIH) have found new insights into how sensations like heat and touch are transformed into brain signals, and how inflammation alters these signals to cause pain. This study concentrates on somatosensory neurons in the skin, which help locate and gauge touch's intensity and emotional quality. Using advanced imaging and molecular analysis, the study investigated how different receptor cells in mice respond to heat and touch stimuli.
"To develop better treatments for pain, it’s critical that we deepen our understanding of the biology behind how sensory signals are received, transmitted, and ultimately perceived by the brain," said Alex Chesler, Ph.D., co-author of the study and senior investigator at NIH. "Over the past few years, we developed a platform for watching sensation in action, revealing new details about the cells and molecules required and, in this study, how inflammation triggers pain."
The findings illustrate how cells are activated based on whether the stimulus is mild or harmful. Heat and gentle touch were processed by distinct cell types. As stimulus intensity increased, overlaps occurred in the nerve cells responsible for transmitting these sensations, explaining how cells distinguish between harmless and harmful stimuli.
While inflammation is related to pain, the cellular and molecular processes remained unclear. By injecting prostaglandin E2, an inflammation-inducing molecule, into the skin, researchers found that pain signaling neurons became active and sensitive to heat, revealing the ongoing cellular processes.
"This explains how inflammation drives ongoing pain and why heat becomes more painful," said Nick Ryba, Ph.D., co-author and senior investigator at NIH. "However, what was unexpected was that touch detection remained unchanged."
The study also found inflammation-induced hypersensitivity to touch, or tactile allodynia, results from continuous pain signaling overlapping with normal touch sensation. Prior NIH research showed that the ion channel PIEZO2 is crucial in this form of pain.
Drs. Chesler and Ryba's teams collaborate on research about sensory input detection and processing by the brain. Dr. Chesler noted that although this study focused on mice, the neural similarities to humans make these findings significant.
"By learning more about how touch and heat are signaled in the body, we’re identifying new clues for treating pain," said Dr. Chesler. "Our study shows how different types of pain may benefit from different types of treatments. In short, by identifying exactly which cells and molecules ‘turn up the volume’ of different types of pain, we may be able to identify the ‘switches’ that can turn the volume down."
The study was led by NIH’s Sensory Cells and Circuits Lab and the Taste and Smell Section's investigators.
The National Center for Complementary and Integrative Health (NCCIH) aims to rigorously investigate complementary health approaches for safety and efficacy. For more details, visit their website.
The National Institutes of Health (NIH) is a principal U.S. medical research agency, supporting a wide spectrum of health research. More information can be found on their website.
Ghitani N., von Buchholtz L.J., MacDonald D.I., Falgairolle M., Nguyen M.Q., Licholai J.A., Ryba N.J.P., Chesler A.T. A distributed code across nociceptor classes for thermosensation and inflammatory pain. Nature. DOI: 10.1038/s41586-025-08875-6.
